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Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin

Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel
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Academic Editor: Daniel Gillet
Toxins 2015, 7(11), 4817-4831; https://doi.org/10.3390/toxins7114817
Received: 13 October 2015 / Revised: 2 November 2015 / Accepted: 11 November 2015 / Published: 17 November 2015
Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice intranasally exposed to the toxin and revealed multi-phasic cell-type-dependent binding profiles. While macrophages (MΦs) and dendritic cells (DCs) displayed biphasic binding to ricin, monophasic binding patterns were observed for other cell types; epithelial cells displayed early binding, while B cells and endothelial cells bound toxin late after intoxication. Neutrophils, which were massively recruited to the intoxicated lung, were refractive to toxin binding. Although epithelial cells bound ricin as early as MΦs and DCs, their rates of elimination differed considerably; a reduction in epithelial cell counts occurred late after intoxication and was restricted to alveolar type II cells only. The differential binding and cell-elimination patterns observed may stem from dissimilar accessibility of the toxin to different cells in the lung and may also reflect unequal interactions of the toxin with different cell-surface receptors. The multifaceted interactions observed in this study between ricin and the various cells of the target organ should be considered in the future development of efficient post-exposure countermeasures against ricin intoxication. View Full-Text
Keywords: ricin; lung; binding; macrophages; epithelial cells; alveolar type II cells ricin; lung; binding; macrophages; epithelial cells; alveolar type II cells
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Sapoznikov, A.; Falach, R.; Mazor, O.; Alcalay, R.; Gal, Y.; Seliger, N.; Sabo, T.; Kronman, C. Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin. Toxins 2015, 7, 4817-4831.

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